RIFABUTIN

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Inhibits DNA-dependent RNA polymerase in susceptible bacteria, blocking RNA synthesis.

What the body does with it

Metabolism	Hepatic, via CYP3A4
Excretion	Renal (53% as unchanged drug and metabolites), fecal (30%), with biliary excretion contributing to enterohepatic recycling.
Half-life	45 hours (range 32-67 hours) in adults; terminal elimination half-life decreases to 17 hours after repeated dosing due to autoinduction of metabolism.
Protein binding	71% (primarily to albumin, with moderate affinity to alpha-1-acid glycoprotein).
Volume of Distribution	8.6 L/kg (mean); extensive tissue distribution with high intracellular penetration, especially in macrophages and neutrophils.
Bioavailability	Oral: 85% (relative to intravenous); food reduces peak concentration by 17% but does not affect AUC.
Onset of Action	Oral: 2-4 hours for antimycobacterial effect; intravenous: immediate systemic exposure, clinical effect within 24-48 hours.
Duration of Action	24 hours; sustained tissue concentrations due to long half-life, with once-daily dosing sufficient for prophylaxis.

Classification & Brands

Dosing & administration

300 mg orally once daily. For Mycobacterium avium complex (MAC) prophylaxis, 300 mg once daily. For active tuberculosis (in combination therapy), 5 mg/kg (up to 300 mg) orally once daily or 5 times weekly.

Dosage form	CAPSULE
Renal impairment	For CrCl < 30 mL/min: reduce dose by 50% (e.g., 150 mg once daily). For patients on hemodialysis: no supplemental dose required, but administer after dialysis if anuric.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B or C: reduce dose by 50% (e.g., 150 mg once daily) and monitor for toxicity. No specific guidelines for severe hepatic impairment; use caution.
Pediatric use	Neonates: not recommended. Infants and children: 5 mg/kg orally once daily (maximum 300 mg) for MAC prophylaxis; for tuberculosis, 5-10 mg/kg (max 300 mg) once daily or 5 times weekly. Safety and efficacy not established in children <1 year.
Geriatric use	No specific dose adjustment required for age alone; consider renal function (CrCl) as elderly often have reduced renal clearance. Monitor for adverse effects (e.g., neutropenia, uveitis) due to potential age-related changes.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Induces CYP3A4 decreasing levels of many drugs Can cause uveitis and neutropenia.

Breastfeeding	Rifabutin is excreted into human breast milk; M/P ratio is not determined. Based on limited data, infant exposure is estimated to be low (less than 1% of maternal weight-adjusted dose). Caution is advised; consider the benefits of breastfeeding and the risk of infant exposure. Monitor infant for jaundice, vomiting, and diarrhea.
Teratogenic Risk	Rifabutin is not teratogenic in animal studies at doses up to 40 mg/kg/day in rats and 20 mg/kg/day in rabbits, with no evidence of fetal harm. Human data are limited; no increased risk of major malformations has been reported. However, due to its mechanism (inhibition of bacterial RNA polymerase), theoretical risk cannot be excluded. Use during pregnancy only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Neutropenia
Serious Effects

Absolute Contraindications

["Hypersensitivity to rifabutin or any rifamycins","Concurrent use of delavirdine or saquinavir/ritonavir"]

Clinical Precautions

Precautions

["Hepatotoxicity","Uveitis","Neutropenia","Thrombocytopenia","Hypersensitivity reactions","Drug interactions (especially with CYP3A4 substrates/inhibitors)","Resistance development"]

Clinical Tips & Counseling

Drug interactions

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